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(Hypertension. 2007;49:e48.)
© 2007 American Heart Association, Inc.

Letters to the Editor

Response to Type 2 Deiodinase Thr92Ala Polymorphism Is Not Associated With Arterial Hypertension in Type 2 Diabetes Mellitus Patients

Olga Gumieniak; Gordon H. Williams

Endocrinology, Diabetes, and Hypertension Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical, School, Boston, Mass

Canani et al¹ reported that a type 2 iodothyronine deiodinase (Dio2) nonsynonymous polymorphism, threonine 92 to alanine (Thr92Ala), was not associated with arterial hypertension in 315 patients with type 2 diabetes mellitus. We have recently reported that among euthyroid adults not on thyroid hormone replacement therapy the common Ala92 Dio2 allele approximately doubles the risk for the development of hypertension in 372 hypertensive and normotensive subjects.²

We agree with Canani and colleagues that the discrepant results of the 2 studies may be explained by the differences in populations studied: patients with type 2 diabetes mellitus versus carefully selected patients with mild to moderate essential hypertension without any major comorbidities.

Essential hypertension is a complex heterogeneous trait caused by interplay between genetic and environmental factors, resulting in individual hypertensive patients having unique combinations of genes contributing to their blood pressure elevation. However, within the heterogeneous population of hypertensive patients, more genetically homogeneous subgroups (intermediate phenotypes) can be identified, defined by a common physiological or phenotypic trait that is used to focus genetic investigation.^3,4,5 Type 2 diabetes mellitus is also a complex genetic disorder with a variety of genetic and environmental factors contributing to the common phenotype of hyperglycemia.⁶ It is, therefore, likely that pathogenesis and genetic determinants of hypertension in patients with type 2 diabetes mellitus differ from those in patients developing essential hypertension in the absence of type 2 diabetes.

Results of our study support an important role for genetic variation in the hypothalamic-pituitary-thyroid pathway in influencing susceptibility to hypertension. Further work is needed to uncover the mechanisms by which Dio2 may affect hypertension susceptibility, and to define subgroups of hypertensive patients where the effect of Dio2 is most relevant.

	Acknowledgments

 
Disclosures

None.

	References

Top References

 

1. Canani LH, Leie MA, Machado WE, Capp C, Maia AL. Type 2 deiodinase Thr92Ala polymorphism is not associated with arterial hypertension in type 2 diabetes mellitus patients. Hypertension. 2007; 49: e47.[Free Full Text]
2. Gumieniak O, Perlstein TS, Williams JS, Hopkins PN, Brown NJ, Raby BA, Williams GH. Ala92 type 2 deiodinase allele increases risk for the development of hypertension. Hypertension. 2007; 49: 461–466.[Abstract/Free Full Text]
3. Williams GH. Genetic factors associated with volume-sensitive hypertension. Mol Cell Endocrinol. 2004; 217: 41–44.[CrossRef][Medline] [Order article via Infotrieve]
4. Lalouel J. Large-scale search for genes predisposing to essential hypertension. Am J Hypertens. 2003; 16: 163–166.[CrossRef][Medline] [Order article via Infotrieve]
5. Kosachunhanun N, Hunt SC, Hopkins PN, Williams RR, Jeunemaitre X, Corvol P, Ferri C, Mortensen RM, Hollenberg NK, Williams GH. Genetic determinants of nonmodulating hypertension. Hypertension. 2003; 42: 901–908.[Abstract/Free Full Text]
6. Freeman H, Cox RD. Type-2 diabetes: a cocktail of genetic discovery. Human Molecular Genetics. 2006; 15: R202–R209.[Abstract/Free Full Text]

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This Article Full Text (PDF) All Versions of this Article: 49/6/e48    most recent HYPERTENSIONAHA.107.088559v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gumieniak, O. Articles by Williams, G. H. Search for Related Content PubMed PubMed Citation Articles by Gumieniak, O. Articles by Williams, G. H. Related Collections Clinical genetics Clinical Studies